(i) Field of the Invention
The invention relates to novel pharmaceutical compounds and more particularly to controlled substances that are covalently bound to a chemical moiety and thus rendered pharmaceutically inactive until broken down by enzymatic and/or chemical means in a time-dependent manner following oral administration. Delayed release from the conjugate prevents spiking of drug levels and affords gradual release over an extended period of time. The enzymatic and/or chemical conditions necessary for the release of the controlled substance are either not present or of minimal activity when the novel pharmaceutical compound is introduced nasally, inhaled, or injected; thus, also preventing spiking when administered by these routes. Controlled substances with these novel properties are less likely to be abused due to the diminished “rush” effect of the modified controlled substance. Consequently, the therapeutic value of these pharmaceuticals is enhanced by decreasing euphoria while increasing the duration of the analgesic effect.
(ii) Description of the Related Art
A number of pharmacologically useful compounds are also commonly abused controlled substances. In particular, analgesics that are prescribed for the management of acute and chronic pain have become increasingly abused over the last decades. For example, the increase in prescription of oxycodone in the last few years led to widespread abuse of this drug in certain areas of the U.S. Amphetamines are another example of controlled substances with important pharmacological uses that also are highly addictive and commonly abused. There has been considerable effort in research to develop new compounds with the pharmacological benefits of these drugs, but that are less addictive or less likely to be abused.
The need for “street safe” narcotics was highlighted recently by the epidemic of problems associated with the long-acting analgesic OxyContin, an extended release form of oxycodone. Numerous media reports described the rapidly growing frequency of abuse of this potent narcotic which contains high levels of oxycodone formulated into an extended release matrix. The problem was summarized recently in the following extract from a web page of the National Institute for Drug Abuse (NIDA):                A variety of sources, including NIDA's own Community Epidemiology Work Group, a network of epidemiologists and researchers from 21 major U.S. metropolitan areas who monitor and report on community-level trends in drug abuse, are finding that people are “short circuiting” the time-release form of this medication by chewing, crushing, or dissolving the pills. Chewing or crushing the prescription drug corrupts or foils its time-release protection, enabling the users to experience a rapid and intense euphoria that does not occur when taken as designed and prescribed. Once having crushed the pills, the individuals are injecting, inhaling, or taking them orally, often with other pills, marijuana, or alcohol.        
Although the injecting and “snorting” routes of administration are most associated with drug abuse “a Drug Enforcement Administration (DEA) study found that the vast majority of 110 people identified in the previous two years as having overdosed on OxyContin took the drug orally as opposed to snorting or injecting a crushed tablet (see ADAW, Nov. 19, 2001). Rapid release of the medication in people who are not tolerant can be fatal.”